| GDP dissociation inhibitor D4-GDI (Rho-GDI 2), but not the homologous rho-GDI 1, is cleaved by caspase-3 during drug-induced apoptosis. | |
| | |
MedLine Citation:
|
PMID: 10698706 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Different cytotoxic drugs induce cell death by activating the apoptotic programme; a family of cysteinyl aspartate proteases named caspases has been shown to be involved in the initiation as well as the execution of this kind of cell death. In the present study, cleavage of D4-GDI (Rho-GDI 2), an abundant haemopoietic-cell GDP dissociation inhibitor for the Ras-related Rho family GTPases, was demonstrated after treatment of BJAB Burkitt-like lymphoma cells with taxol or epirubicin. The cleavage of D4-GDI occurred simultaneously with the activation of caspase-3 but preceded DNA fragmentation and the morphological changes associated with apoptotic cell death. By using high-resolution two-dimensional gel electrophoresis it was shown that this cleavage is specific: whereas the level of the homologous protein Rho-GDI 1 was not significantly altered during drug-induced apoptosis and in cytochrome c/dATP-activated cellular extracts, D4-GDI disappeared owing to proteolytic cleavage. Inhibitor experiments with Z-DEVD-fmk (in which Z stands for benzyloxycarbonyl and fmk for fluoromethyl ketone) and microsequencing of the D4-GDI fragment revealed that this occurs at the caspase-3 cleavage site. Our results strongly suggest the differential regulation of the homologous GDP dissociation inhibitors Rho-GDI 1 and D4-GDI during drug-induced apoptosis by proteolysis mediated by caspase-3 but not by caspase-1. Owing to their crucial role as modulators of Rho GTPases, this might in turn have a significant impact on the mechanisms that induce the cytoskeletal and morphological changes in apoptotic cells. |
| | |
Authors:
|
F Essmann; T Wieder; A Otto; E C Müller; B Dörken; P T Daniel |
Related Documents
:
|
14581476 - Selective disruption of lysosomes in hela cells triggers apoptosis mediated by cleavage... 12893746 - Cathepsin-b-dependent apoptosis triggered by antithymocyte globulins: a novel mechanism... 11943196 - Caspase-3 is not essential for dna fragmentation in mcf-7 cells during apoptosis induce... 21060756 - Time dependent bladder apoptosis induced by acute bladder outlet obstruction and subseq... 15674346 - Arsenic trioxide triggers a regulated form of caspase-independent necrotic cell death v... 10821786 - Retinoid-mediated inhibition of interleukin-12 production in mouse macrophages suppress... |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: The Biochemical journal Volume: 346 Pt 3 ISSN: 0264-6021 ISO Abbreviation: Biochem. J. Publication Date: 2000 Mar |
Date Detail:
|
Created Date: 2000-05-04 Completed Date: 2000-05-04 Revised Date: 2009-11-18 |
Medline Journal Info:
|
Nlm Unique ID: 2984726R Medline TA: Biochem J Country: ENGLAND |
Other Details:
|
Languages: eng Pagination: 777-83 Citation Subset: IM |
Affiliation:
|
Department of Hematology, University Medical Center Charité, Campus Berlin-Buch, Lindenberger Weg 80, 13125 Berlin, Germany. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Amino Acid Sequence Apoptosis / drug effects* Caspase 3 Caspases / metabolism* Cell Line Electrophoresis, Gel, Two-Dimensional Enzyme Activation Guanine Nucleotide Dissociation Inhibitors / metabolism* Hydrolysis Mass Spectrometry Molecular Sequence Data Protein Isoforms / metabolism* Sequence Homology, Amino Acid |
| Chemical | |
Reg. No./Substance:
|
0/Guanine Nucleotide Dissociation Inhibitors; 0/Protein Isoforms; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Allosteric regulation of neuronal nitric oxide synthase by tetrahydrobiopterin and suppression of au...
Next Document: Altered toxicity of the prion protein peptide PrP106-126 carrying the Ala(117)-->Val mutation.